Open AccessPotassium Regulates IL-1β Processing Via Calcium-Independent Phospholipase A2
Author(s) -
Iwan Walev,
Jochen Klein,
Matthias Husmann,
Angela Valeva,
Susanne Strauch,
H Wirtz,
Oksana Weichel,
Sucharit Bhakdi
Publication year - 2000
Publication title -
the journal of immunology/the journal of immunology
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.164.10.5120
Subject(s) - phospholipase a2 , phospholipase , phospholipase a , beta (programming language) , microbiology and biotechnology , chemistry , biochemistry , enzyme , biology , computer science , programming language
We report that potassium leakage from cells leads to activation of the Ca2+-independent phospholipase A2 (iPLA2), and the latter plays a pivotal role in regulating the cleavage of pro-IL-1 beta by the IL-converting enzyme caspase-1 in human monocytes. K+ efflux led to increases of cellular levels of glycerophosphocholine, an unambiguous indicator of phospholipase A2 activation. Both maturation of IL-1 beta and formation of glycerophosphocholine were blocked by bromoenol lactone, the specific iPLA2 inhibitor. Bromoenol lactone-dependent inhibition of IL-1 beta processing was not due to perturbation of the export machinery for pro-IL-1 beta and IL-1 beta or to caspase-1 suppression. Conspicuously, activation of Ca2+-dependent phospholipase A2 did not support but rather suppressed IL-1 beta processing. Thus, our findings reveal a specific role for iPLA2 activation in the sequence of events underlying IL-1 beta maturation.